Study reveals new treatment to reverse inflammation and arterial blockages in rheumatoid arthritis

Researchers at Queen Mary University of London have discovered that the RvT4 molecule strengthens the body’s natural defenses against atherosclerosis (hardening of the arteries) in patients with rheumatoid arthritis.

Mouse studies undertaken by researchers at the William Harvey Research Institute and the Center for Inflammation and Therapeutic Innovation at Queen Mary University of London show that increasing levels of the RvT4 molecule in the body improves the capacity of the mechanisms of the body’s defense (macrophages) to reduce local inflammation. and clear blockages in blood vessels. This advance in understanding the processes involved could lead to better treatments for people with rheumatoid arthritis (RA) who are at higher risk of developing cardiovascular disease.

Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis in the UK, affecting around 1% of the population. About 10,000 people are diagnosed with RA each year. In addition to the better-known symptoms of joint inflammation, people with this condition are also twice as likely as others to develop blood vessel disease. This can lead to serious complications and an increased risk of premature death.

One type of blood vessel disease seen in people with RA is atherosclerosis, which is caused by a buildup of fatty material called “plaque” along the walls of the arteries. This buildup causes the arteries to harden and narrow, making it more difficult for blood to flow through the body. These blockages can also release, causing heart attacks and strokes. Understanding why RA patients are at increased risk for these cardiovascular problems is essential to developing better treatments for this group and others.

To better understand the causes of blood vessel disease in RA patients, researchers explored the role of a group of molecules called series 13 resolvins (RvTs). In experimental arthritis, levels of one of these molecules, RvT4, are markedly reduced, a phenomenon associated with a greater degree of blood vessel disease. This study was designed to explore why this might be the case.

Published in Natural communicationsthe study found that treating arthritic mice with RvT4 reduced blood vessel inflammation by reprogramming macrophages (a group of white blood cells that accumulate in diseased vessels) to release stored lipids.

The researchers observed that these lipids prevented macrophages from doing their usual job of removing dead cells and reducing localized inflammation in blood vessels. Once freed from their lipid burden, the macrophages were able to move and work much more efficiently to reduce the causes of atherosclerosis. The observation that RvT4 restores the protective biological activities of macrophages is an exciting finding.

RA patients also often have metabolic dysfunction, which could exacerbate vascular diseases. The study found that administration of RvT4 to mice engineered to develop features of metabolic dysfunction, advanced atherosclerosis, and arthritis resulted in an overall decrease in plasma lipoprotein-associated cholesterol and an increase in the ratio between cholesterol associated with HDL and total cholesterol.

Jesmond Dalli, Professor of Molecular Pharmacology and Director of the Lipid Mediators Unit at the William Harvey Institute at Queen Mary University of London, said: “The study is important because it identifies for the first time the loss of lipid production. RvT4 as a new potential cause of blood problems. blood vessel inflammation in the context of arthritis, providing a mechanistic explanation for the cause of this important disease in RA patients. It also showed that RvT4 restores the biological activities of lipid-laden macrophages by promoting the degradation and efflux of lipids from cells, an observation that may guide the development of new treatments to limit the incidence and/or severity of diseases. cardiovascular problems in patients with RA.

Victoria King, director of funding and impact at Barts Charity, said: “This exciting new discovery helps to explain why some patients with rheumatoid arthritis are more likely to develop blood vessel disease. This could pave the way for the development of new treatments for these patients. to help them live longer and healthier lives.

The deregulation of the biological responses of macrophages by the accumulation of lipids is also involved in the appearance and development of many other pathologies, notably obesity. Drugs derived from RvT4 or RvT4-based compounds may therefore be useful in limiting inflammation and promoting the release of accumulated lipids from macrophages in patients suffering from a number of other pathologies.